New antimalarial compound discovered
A study published in Nature develops a chemical that is effective against the deadly Plasmodium falciparum parasite at several stages of its life cycle. The chemical, DDD107498, was found during a screen of University of Dundee's library of compounds for drug discovery. Genetic approaches identified the target of the compound, which is a part of the parasite's biology that has not been attacked by previous drugs. Researchers therefore believe it has great potential to work against current drug-resistant parasites.
"The publication describes the discovery and profiling of this exciting new compound. It reveals that DDD107498 has the potential to treat malaria with a single dose, prevent the spread of malaria from infected people, and protect a person from developing the disease in the first place."
Professor Ian Gilbert, Head of Chemistry at the Drug Discovery University of Dundee, who led the team that discovered the compound
"There is still some way to go before the compound can be given to patients. However, we are very excited by the progress that we have made."
The compound was identified through a collaboration between the University of Dundee's Drug Discovery Unit (DDU) and Medicines for Malaria Venture (MMV), working with a team from the Wellcome Trust Sanger Institute.
To learn how the compound works, Dr Marcus Lee from Columbia University College of Physicians and Surgeons, who joins the Sanger Institute Malaria Programme faculty this month, developed malaria parasites in the lab that were resistant to DDD107498. This was done by growing malaria parasites in the lab and gradually increasing the dose of the compound that they were exposed to.
Researchers at the Sanger Institute then analysed the genomes of the resistant parasites and compared them with the genomes of drug sensitive lines to find out which genes had changed to confer resistance. The gene PfeEF2 was singled out in this comparison, which is involved in how the parasite synthesises new proteins.
New antimalarial drugs are needed urgently as emerging strains in South Asia are now resistant to artemisinin, the most effective drug currently available. Researchers fear that this resistance may develop in Africa or spread to Africa, where this drug is widely used.
"Drug resistance is one of the critical problems facing malaria control, and is a problem that we are deeply interested in. This exciting compound targets a completely new pathway, giving us hope that it will offer a different avenue of attack to current antimalarial drugs."
Dr Julian Rayner, a senior author from the Malaria Programme at the Sanger Institute
"Our partnership with MMV was critical to the progress of this compound. Dr Paul Willis at MMV and Sir Simon Campbell, a mentor from MMV's Expert Scientific Advisory Committee, gave invaluable input to the project. We have extensively profiled the compound, investigating its properties to understand how it works; this could not have been done without MMV's scientific input and support of its network of partners around the world."
Professor Ian Gilbert